Alcoholism

Alcoholism, or alcohol dependence - chronic excessive consumption, consisting in compulsive alcoholization, growing tolerance, withdrawal symptoms. 

Excessive consumption of alcohol can lead to severe physical and mental problems. 

[1], [2], [3], [4]

Epidemiology

About 2/3 of American adults consume alcohol. The ratio of men to women is 4: 1. The prevalence of alcohol and alcohol abuse throughout life is about 15%.

People who abuse alcohol and addicted to it usually have serious social problems. Frequent intoxication is obvious and destructive, it interferes with the ability to socialize and work. Thus, drunkenness and alcoholism can lead to the destruction of social ties, the loss of work due to absenteeism. In addition, due to drunkenness, a person may be arrested, delayed for driving under the influence of alcohol, which exacerbates the social consequences of alcohol consumption. In the United States, the concentration of alcohol in the blood, permissible for driving, in most states is £ 80 mg / dL (0.08%).

Women who suffer from alcoholism tend to drink more often alone and less often are socially stigmatized. Patients who have alcoholism can seek medical help in the treatment of their drunkenness. Ultimately, they can be hospitalized with alcoholic delirium or cirrhosis of the liver. They often get injured. The earlier this behavior becomes apparent throughout life, the worse the disorder.

The occurrence of such a disease as alcoholism is higher in the biological children of parents who suffer from alcoholism than in the adopted children, the percentage of children from alcoholic parents who have problems with alcohol use is higher than in the general population. Accordingly, in some populations and countries the prevalence of alcoholism is higher. There is evidence of a genetic or biochemical predisposition, including evidence that some people who became alcoholics developed into intoxication more slowly, i.e. They had a higher threshold of alcohol effects on the central nervous system.

Details about the prevalence and statistics of alcoholism in different countries of the world can be read here.

[5], [6], [7],

Causes of the alcoholism

Alcoholism is a disease so ancient that even the date of 8000 years BC, when the alcoholic drink is mentioned for the first time, is not accurate. Judging by the extent of the spread of alcoholism, it seems that this is a disease in the blood of almost half of the world's population since the time of Adam and Eve. It's not about drinking culture, it's a separate topic for discussion. The problem is that this culture is disappearing, and total alcoholism is moving in its place by leaps and bounds. Judge for yourselves: according to the UN standards, drinking alcohol over nine liters per year is considered a disease. Are there many people who adhere to these norms? Alcoholism develops imperceptibly, and when it passes into a menacing stage, such a stable dependence is formed that it can certainly be cured, but it is extremely difficult and a long period is needed. The problem lies in the fact that the person who is alcohol-dependent does not admit his illness stubbornly, in the main, close people beat the alarm. This, perhaps, explains the low percentage of the cure of alcohol dependence - in fact most often the patient is simply forced to consult a doctor, and his personal motivation in this process almost always tends to zero.

Alcohol abuse is usually understood as the uncontrolled use of alcohol, leading to inability to fulfill its obligations, to find in a dangerous situation, problems with the law, social and interpersonal difficulties, while there is no data for dependence.

Alcoholism is the frequent consumption of large amounts of alcohol, leading to tolerance, mental and physical dependence and a dangerous withdrawal syndrome. The term "alcoholism" is often used as a synonym for alcohol dependence, especially if the use of alcohol leads to clinically pronounced toxic effects and tissue damage.

The use of alcohol to the level of intoxication or the formation of maladaptive styles of alcohol consumption, leading to abuse, begins with the desire to achieve pleasant sensations. Some of those who consume alcohol and enjoy it then tend to repeat this state periodically.

Those who constantly drink alcohol or become dependent on it, some personality traits are more pronounced: isolation, loneliness, shyness, depression, dependence, hostility and autodestructive impulsiveness, sexual immaturity. Alcoholism often comes from broken families, these alcoholics have broken relationships with their parents. Social factors transmitted through culture and upbringing affect the characteristics of alcohol use and subsequent behavior.

[8], [9],

Pathogenesis

Alcohol refers to drugs that depress the central nervous system, because it has a sedative effect and causes drowsiness. Nevertheless, the initial effect of alcohol, especially in low doses, is often of a stimulating nature, probably due to inhibition of the inhibitory systems. Volunteers, who had only a sedative effect after taking alcohol, did not return to him with free choice. More recently, it has been shown that alcohol enhances the action of the inhibitory mediator gamma-aminobutyric acid (GABA) on a certain subpopulation of GABA receptors. In addition, ethanol is able to increase the activity of dopaminergic neurons of the ventral tire, projecting onto the adjacent nucleus, which leads to an increase in the level of extracellular dopamine in the ventral striatum. This activation can be mediated via GABA receptors and suppression of inhibitory neurons. It is shown that this effect is fixed as the rats are trained to receive alcohol. At the same time, the level of dopamine in the region of the adjacent nucleus increases as soon as the rats are placed in a cage where they previously received alcohol. Thus, one of the pharmacological effects of alcohol - increasing the level of extracellular dopamine in the nucleus adjacent to it - is similar to the action of other addictive substances - cocaine, heroin, nicotine.

There is evidence of the involvement of the endogenous opioid system in the reinforcing effect of alcohol. In a series of experiments it was shown that animals trained to receive alcohol cease to take the necessary actions for this purpose after the administration of opioid receptor antagonists of naloxone or naltrexone. These data are consistent with the results obtained recently and in the study of alcoholics - against the background of the introduction of a long-acting antagonist of opioid receptors of naltrexone, the feeling of euphoria with alcohol intake is weakened. The intake of alcohol in the laboratory causes a significant increase in the level of peripheral beta-endorphin only in volunteers who had cases of alcoholism in the family history. There are also data on the involvement of the serotonergic system in providing a reinforcing effect of alcohol. It is possible that alcohol, reaching the central nervous system at a relatively high concentration and influencing the fluidity of the cell membrane, can affect several neurotransmitter systems. Accordingly, there may be several mechanisms for the development of euphoria and dependence.

Alcohol weakens memory for recent events and, in high concentrations, causes "dips" in memory when circumstances and actions disappear from memory during intoxication. The mechanism of influence on memory is unclear, but experience shows that patients' reports about the causes of alcohol consumption and their actions in a state of intoxication are untrue. Alcoholics often claim that they drink in order to alleviate anxiety and depression. Nevertheless, observations show that they usually become more dysphoric as the drunk dose increases, which contradicts the explanation given above.

[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21],

Symptoms of the alcoholism

Alcoholism is considered a serious illness, with chronic long-term course, which begins secretly, asymptomatically, and it can be very sad to end.

Signs of acute alcohol intoxication

Alcohol is absorbed into the blood mainly from the small intestine. It accumulates in the blood, as absorption occurs faster than oxidation and elimination. From 5 to 10% of consumed alcohol is excreted unchanged in urine, then, exhaled air; the rest is oxidized to CO ₂ and water at a rate of 5-10 ml / h of absolute alcohol; each milliliter gives about 7 kcal. Alcohol is mainly a CNS depressant.

At a blood alcohol concentration of about 50 mg / dL sedation or soothing develops; at a concentration of 50 to 150 mg / dL - impaired coordination; 150 - 200 mg / dl - delirium; the concentration of 300-400 mg / dL leads to loss of consciousness. Concentration of more than 400 mg / dL can be lethal. With the rapid use of large amounts of alcohol, sudden death may occur due to respiratory depression or arrhythmia. These problems arise in US colleges, but also in other countries where this syndrome is more common.

[22]

Signs of chronic alcoholism

Patients who often consume large amounts of alcohol become tolerant to its effects, i.e. In the end, the same amount of substance leads to less intoxication. Tolerance is caused by adaptive changes in CNS cells (cellular or pharmacodynamic tolerance). In patients who developed tolerance, there may be an unbelievably high concentration of alcohol in the blood. On the other hand, tolerance to alcohol is incomplete, and a certain degree of intoxication and damage is observed at sufficiently high dosages. Even patients with high tolerance may die due to the suppression of the respiratory center, secondary to an alcohol overdose. Patients with developed tolerance are susceptible to alcoholic ketoacidosis, especially during drinking-bouts. Patients develop cross-tolerance to many other CNS depressants (eg, barbiturates, sedatives of other structures, benzodiazepines).

The physical dependence accompanying tolerance is strong, and therefore in a state of cancellation, potentially lethal adverse effects may develop. Alcoholism ultimately leads to organ damage, more often to hepatitis and cirrhosis, gastritis, pancreatitis, cardiomyopathy, often accompanied by arrhythmias, peripheral neuropathy, brain damage [including Wernicke's encephalopathy, Korsakov's psychosis, Marietaafa-Binyamy's disease and alcoholic dementia].

Signs and symptoms accompanying alcohol withdrawal usually appear 12-48 hours after discontinuation of use. The mild cancellation syndrome is manifested by tremors, weakness, sweating, hyperreflexia and gastrointestinal symptoms. Some patients develop tonic-clonic seizures, but usually no more than 2 seizures in a row (alcoholic epilepsy).

Symptoms of alcohol dependence

Almost all people experienced mild alcohol intoxication, but its manifestations are extremely individual. In some people there is only a violation of coordination of movements and drowsiness. Others become excited and talkative. As the concentration of alcohol in the blood increases, the sedative effect increases until the coma develops. At a very high concentration of alcohol, a lethal outcome occurs. The initial sensitivity (innate tolerance) to alcohol varies significantly and correlates with the presence of cases of alcoholism in the family history. A person with a low sensitivity to alcohol can tolerate large doses even at the first use, without disturbing coordination or other symptoms of intoxication. As already indicated, it is these people who are predisposed to the development of alcoholism in the future. With repeated use, tolerance can gradually increase (the acquired tolerance), so even with a high level of alcohol in the blood (300-400 mg / dl), alcoholics do not look drunk. However, the lethal dose does not increase in proportion to the tolerance to sedation, and thus, the safe dose range (therapeutic index) narrows.

With drunken alcohol consumption, not only the acquired tolerance develops, but physical dependence also inevitably arises. A person is forced to alcoholize in the morning to restore the level of alcohol in the blood, which fell due to the fact that a significant part of alcohol was metabolized overnight. Over time, these individuals can wake up in the middle of the night and drink to avoid anxiety caused by low levels of alcohol. Alcohol abstinence syndrome, as a rule, depends on the average daily dose and is usually stopped by the introduction of alcohol. The withdrawal symptoms are frequent, but as a rule, they are not severe by themselves and do not threaten life unless other problems, such as infection, trauma, eating disorders or electrolyte balance, are added. In such situations, white delirium tremens can arise.

Signs of an alcoholic hallucinosis

Alcoholic hallucinosis develops after a sharp cessation of prolonged and excessive consumption of alcohol. Symptoms include auditory illusions and hallucinations often of an accusing and menacing nature; patients are often anxious and frightened by hallucinations and bright, frightening dreams. This syndrome may have a similarity to schizophrenia, although thinking is usually not broken and there is no typical history of schizophrenia. Symptoms do not look like a delirious state with acute organic brain syndrome, as well as alcohol delirium and other pathological reactions associated with cancellation. Consciousness remains clear, and usually there are no symptoms of autonomic lability, characteristic of alcoholic delirium. When there is a hallucinosis, it usually follows an alcoholic delirium and is short-lived. Recovery usually occurs between the 1 st and 3 rd weeks; Relapses are possible if the patient resumes the use of alcohol.

Signs of alcoholic delirium

Alcohol delirium usually begins 48-72 hours after alcohol withdrawal from anxiety attacks, increasing confusion, sleep disturbances (accompanied by frightening dreams and night illusions), severe hyperhidrosis and deep depression. Typical are fleeting hallucinations that cause anxiety, fear and even horror. Typical for the onset of alcoholic delirium, confusion and disorientation can go into a state where the patient often imagines that he is at work and is engaged in his usual business. Vegetative lability, manifested by sweating, rapid pulse, rising temperature, accompanies delirium and progresses with it. The slight form of delirium is usually accompanied by severe sweating, a heart rate of 100-120 beats per minute, a temperature of 37.2-37.8 "C. A pronounced delirium with gross disorientation and cognitive impairment is accompanied by expressed anxiety, a heart rate of more than 120 beats per minute, temperature above 37.8 ° C.

During the period of alcoholic delirium, the patient may erroneously perceive various stimuli, especially objects in the shadows. Vestibular disturbances can cause the patient to be confident that the floor is moving, the walls are falling, and the room is spinning. As the delirium progresses, a tremor develops in the hands, sometimes spreading to the head and body. Ataxia is expressed; monitoring is necessary to prevent self-harm. Symptoms manifest themselves differently in different patients, but are similar when exacerbations of the same patient.

Symptoms of alcohol withdrawal syndrome

• Increased craving for alcohol
• Tremor, irritability
• Nausea
• Sleep Disorders
• Tachycardia, arterial hypertension
• Sweating
• Hallucinosis
• Epileptic seizures (12-48 hours after the last use of alcohol)
• Delirium (rarely observed with uncomplicated withdrawal syndrome)
• Abrupt excitement
• Confusion of consciousness
• Visual hallucinations
• Fever, tachycardia, profuse sweating
• Nausea, diarrhea

Alcohol causes cross tolerance to other sedative and hypnotic drugs, for example, benzodiazepines. This means that the dose of benzodia zepin for alleviating anxiety in alcoholics should be higher than that of non-drinkers. However, with the combination of alcohol with benzodiazepine, the overall effect is more dangerous than the effect of each drug separately. Benzodiazepines themselves are relatively safe in overdose, but in combination with alcohol they can cause death.

With chronic use of alcohol and other drugs depressing the central nervous system, depression can develop, and the risk of suicide among alcoholics is perhaps the highest in comparison with other categories of patients. Neuropsychological examination of alcoholics in a sober state reveals cognitive impairments, which usually decrease after a few weeks or months of abstinence. More severe memory impairments in recent events are associated with specific brain damage caused by nutritional deficiencies, especially by insufficient intake of thiamine. Alcohol has a toxic effect on many organisms and easily penetrates the placental barrier, causing alcoholic fetal syndrome - one of the most frequent causes of mental retardation.

Stages

Alcoholism has several classical stages.

Alcoholism: stage I (from one year to three to five years): 

• The level of tolerance to any alcohol-containing beverages begins to rise. A person can consume quite a lot of hot drinks, and the signs of intoxication will be the same as those who drink three times less. 
• Develops a real alcoholism at the level of the psyche. If there is no opportunity to drink for any objective reasons, a person shows all his most negative qualities - irritability, aggression and so on. 
• There is no normal reaction of self-defense on the part of the body - a vomitive reflex to intoxication.

Alcoholism: stage II (from five to ten years, depending on the health status and functioning of the protective systems): 

• Classic classic morning abstinence syndromes begin - you want to drink to remove unpleasant symptoms after excessive use the day before. The hangover can be accompanied by typical signs of the second stage - a tremor, a change in personal characteristics (a person is ready to humble himself to get what he wants). Such obsessions (obsessions) are a formidable sign of an entrenched disease. Unlike a healthy person who has overdone with a dose and literally "dies" from all the classic symptoms of intoxication, a patient with alcoholism experiences not just a craving for the next dose, but a passion that is stronger than his mind and body. 
• From the side of the psyche, typical disorder syndromes, disorders of consciousness begin to appear. Sleep, as a rule, superficial, accompanied by nightmarish visions, similar to delusions. Character and personal qualities are already changing more noticeably, so that people around him often say: "He became quite different, unlike himself." Developing sensory disorders - a disorder of vision, hearing. Often a person at this stage becomes extremely suspicious, suspicious, jealous. Psychopathic manifestations can manifest themselves in the form of beliefs that someone is watching or watching a sick person (delusions about persecution). In the second stage delirium (white fever) is not rare. Physiological changes are also already obvious - gastroduodenitis, enlarged spleen, possible hepatitis of alcoholic etiology. The libido decreases (in men the potency is broken), memory is broken, and often speech.

Alcoholism: Stage III (five to ten years): 

• As a rule, this is the terminal stage, unfortunately, during which it is almost impossible to help the patient. Mental disorders are irreversible as well as destruction of internal organs and systems. Cirrhosis, terminal stage of encephalopathy, dementia, visual and auditory nerve atrophy, extensive defeat of the peripheral nervous system do not leave hope not only for recovery, but also do not give chances for survival.

Treatment of the alcoholism

A person is chemically dependent, and that is how a patient is usually called in a medical narcological environment, and should be treated for a long time and in a complex manner. Moreover, it is considered that alcoholism is a systemic disease in the social sense: if a person is surrounded by a family, then ideally all members of the family should attend special sessions, sessions with a psychologist or psychotherapist. These people are considered to be co-addicted to the disease, that is, they are also suffering, only without the participation of spirits.

Undoubtedly, the effectiveness of therapeutic actions depends on the motivation of the patient himself. However much the spouse wishes to save her husband from the addiction, until he understands the whole tragedy of the situation himself, does not want to change his life, all efforts will be reduced only in physiological remission. At the level of the psyche, the dependence will remain at the same level, therefore there are disruptions after drug treatment methods. Ideal conditions for the treatment of patients with alcoholism are specialized medical rehabilitation centers, where the patient must be at least three months, or even more.

The standard methods of treatment are the following stages: 

• Neutralization of withdrawal, detoxification;
• The use of various types of coding, the choice of which depends on the patient's condition, length of use, and also on the psychotype; 
• Attending psychotherapy sessions is the help of a psychologist, a psychotherapist, better if it is a combination of individual therapy and family therapy.

Treatment of acute alcohol intoxication

When people consume alcohol to the level of intoxication, the main task of treatment is to stop consuming any additional amount of alcohol, as this can lead to loss of consciousness and death. The second task is to ensure the safety of the patient and others, not allowing the patient to drive vehicles or to activities that can be dangerous due to alcohol consumption. Calm patients can become anxious and aggressive after lowering the concentration of alcohol in the blood.

Treatment of chronic alcoholism

Medical examination is primarily necessary for the diagnosis of concomitant diseases that can make the withdrawal state worse, and eliminate the CNS lesion, which can hide behind the mask of withdrawal syndrome or mimic it. Symptoms of withdrawal syndrome should be recognized and treated. It is necessary to take steps to prevent the syndrome of Wernicke-Korsakov.

Some drugs used in the state of alcohol withdrawal have similarities in pharmacological effects with alcohol. All patients with withdrawal syndrome can be shown CNS depressants, but not everyone needs it. In many patients, detoxification can be performed without medication, provided that appropriate psychological support is provided, if the environment and the contact itself are safe. On the other hand, these methods may not be available in general hospitals and emergency departments.

The basis for the treatment of alcoholism are benzodiazepines. Their dosage depends on the physical and mental state. In most situations, chlordiazepoxide is recommended in an initial dose of 50-100 mg orally; if necessary, the dose can be repeated twice after 4 hours. Alternatively, diazepam may be used at a dose of 5-10 mg intravenously or orally every hour until sedation is achieved. In comparison with short-acting benzodiazepines (lorazepam, oxazepam) long-acting benzodiazepines (eg, chlordiazepoxide, diazepam) require less frequent administration, and when the dose decreases, their concentration in the blood decreases more evenly. In severe liver diseases, short-acting benzodiazepines (lorazepam) or metabolized by glucuronidase (oxazepam) are preferred. (Note: Benzodiazepines may cause intoxication, physical dependence and withdrawal states in patients with alcoholism, so they should be discontinued after a detoxification period.) Alternatively, carbamazepine 200 mg orally may be used 4 times a day, followed by a gradual cancellation.)

Isolated convulsions do not require specific therapy; with repeated attacks, diazepam 1-3 mg is effective. The abusive use of phenytoin is unnecessary. Outpatient reception of phenytoin almost always is an unnecessary waste of time and medication, as convulsions are observed only in the state of alcohol withdrawal, and heavily drinking or undoing patients do not take anticonvulsants.

Although alcoholic delirium may begin to resolve within 24 hours, it can be lethal, and treatment must begin immediately. Patients with alcoholic delirium are extremely suggestive and respond well to beliefs.

They are usually not subject to physical restraint. The fluid balance should be maintained, it is necessary to immediately give large doses of vitamins B and C, especially thiamine. A significant increase in temperature during alcoholic delirium is a poor prognostic sign. If no improvement is observed within 24 hours, it is possible to suspect the presence of other disorders, such as subdural hematoma, liver and kidney disease or other mental disorders.

Supportive treatment of alcoholism

Maintaining a sober lifestyle is a difficult task. The patient needs to be warned that a few weeks later, when he recovers from the last binge, he may have an excuse for drinking. It is also necessary to say that the patient can try to control alcoholic beverages for several days, less often weeks, but eventually control, as a rule, is lost with time.

Often the best option is to include in the rehabilitation program. Most in-patient rehabilitation programs last 3-4 weeks and are conducted in the center, which is not allowed to leave throughout the course of treatment. Rehabilitation programs combine medical observation and psychotherapy, including individual and group therapy. Psychotherapy includes techniques that enhance motivation and educate patients to avoid the circumstances leading to binge drinking. Important social support for a sober lifestyle, including support for family and friends.

Anonymous alcoholics (AA) are the most successful approach for the treatment of alcoholism. The patient needs to find a group of anonymous alkoglyks, in which he will be comfortable. Anonymous alcoholics provide the patient with non-drinking companions who are always available, as well as the non-drinking environment in which socialization takes place. The patient also hears the confessions of other members of the group about how they explained the reasons for their drunkenness. The help that the patient gives to other alcoholics helps to raise his self-esteem and confidence, in what alcohol helped him earlier. In the United States, unlike other countries, many anonymous alcoglyk groups are included not voluntarily, but by a court decision or on probation. Many patients are reluctant to turn to anonymous alkoglyks, individual counselors or family therapy groups are more suitable for them. For those who are looking for other approaches to treatment, there are alternative organizations, such as "The Life Circle of Recovery" (self-help organizations fighting for sobriety).

Drug treatment for alcoholism

To reduce the symptoms of withdrawal, sedatives with cross-tolerance with alcohol are also introduced. Because of possible damage to the liver, short-acting benzodiazepines should be used, for example, oxazepam, which is prescribed in doses sufficient to prevent or reduce symptoms. In most alcoholics, treatment with oxazepam is advisable to start with a dose of 30-45 mg 4 times a day with an additional intake of 45 mg per night. In the subsequent dose corrected depending on the severity of the condition. The drug is gradually canceled within 5-7 days. After the examination, uncomplicated alcohol abstinence can be effectively treated in an outpatient setting. In the detection of somatic complications or anamnestic indications for epileptic seizures, hospitalization is indicated. To prevent or reverse the development of memory impairments, it is necessary to replenish the deficiency of food and vitamins, primarily thiamine.

Drug treatment for alcoholism should be used in combination with psychotherapy.

Disulfiram disrupts the metabolism of acetaldehyde (an intermediate product of alcohol oxidation), which leads to the accumulation of acetaldehyde. Drinking alcohol for 12 hours after taking disulfiram leads to reddening of the face after 5-15 minutes, then intense face and neck vasodilation, conjunctivitis hyperemia, pulsating headache, tachycardia, hyperpnoea, sweating. When using large doses of alcohol after 30-60 minutes, nausea and vomiting can occur, which can lead to hypotension, dizziness, sometimes to fainting and collapse. The reaction to alcohol can last up to 3 hours. Few patients will take alcohol against the background of disulfiram because of severe discomfort. Also, avoid drugs that contain alcohol (for example, tinctures, elixirs, some solutions for cough and cold, sold without a prescription, which can contain 40% alcohol). Disulfiram is contraindicated in pregnancy and in decompensating cardiovascular diseases. Outpatient, he can be appointed after 4-5 days of abstinence from drinking alcohol. The initial dose of 0.5 g inside 1 time per day for 1-3 weeks, then the maintenance dose is 0.25 g once a day. The effect can last from 3 to 7 days after the last reception. Periodic examinations of the doctor are necessary to support continuation of reception of disulfiram as part of the sobriety program. In general, the use of disulfiram is not established, and many patients do not follow the prescribed treatment. Compliance with such treatment usually requires adequate social support, such as monitoring the intake of the drug.

Naltrexone, an opioid antagonist, reduces the relapse rate in most patients who take it continuously. Naltrexone is taken 50 mg once a day. It is unlikely to be effective without the advice of a doctor. Acamprosate, a synthetic analogue of gamma-aminobutyric acid, is given 2 grams 1 time per day. Acamprosat reduces the level of relapse and the number of days of drinking alcohol if the patient is in a drinking bout; Like naltrexone, it is more effective if it is administered under the supervision of a physician. Nalmefene and the topiromate are currently in the process of studying their ability to reduce cravings for alcohol.

Alcohol abstinence syndrome is a potentially lethal condition. In occasion of mild manifestations of alcohol abstinence, patients usually do not consult a doctor, but in severe cases a general examination, detection and correction of water-electrolyte disorders, deficiency of vitamins, especially the administration of thiamine in a high dose (initial dose of 100 mg IM) is necessary.

Alcoholism is much easier, easier and cheaper to prevent at the earliest stages. For this, of course, we need a system strategy at the state level. But the family can do a lot in this area, it is necessary to start from early childhood - to instil the foundations of a common culture, to bring up the ability to relieve stress in healthy ways - music, sports, create a trusted family environment without distortions towards dictatorship or connivance, permissiveness. The task is difficult, but even more dramatic, and even more tragic can end the life story of a patient with alcoholism.

[23], [24], [25],

Prevention

Detoxification is only the first step on the road to recovery. The goal of long-term treatment is complete abstinence - this is provided mainly by behavioral methods. The possibilities of drugs in facilitating this process are being carefully studied.

[26], [27], [28], [29], [30]

Disulfiram

Disulfiram blocks the metabolism of alcohol, which leads to the accumulation of acetaldehyde, causing a subjectively unpleasant sensation of hot flashes soon after taking alcohol. Knowledge of the possibility of developing this reaction helps the patient stay away from drinking alcohol. Although disulfiram is quite effective from the pharmacological point of view, its clinical effectiveness has not been demonstrated in clinical trials. In practice, many patients stop taking the drug, either because they want to resume taking alcohol, or because they think they no longer need the drug to stay sober. Disulfiram is still used in combination with behavioral techniques, voluntary or mandatory, designed to persuade daily use of the drug. Apparently, in some cases, the drug is useful.

[31], [32], [33], [34], [35], [36], [37]

Naltrexone

Another drug used as an adjuvant in the treatment of alcoholism is naltrexone. Opioid antagonists were first used in opioid dependence. Blocking opioid receptors, they weaken the action of heroin and other opioids. In the following, naloxone (short-acting opioid antagonist) and naltrexone were tested on the experimental model of alcohol dependence. This model is created on rats, who were taught to drink alcohol to avoid electric shock on the paws. Another model was created by selecting individuals who had a predilection for alcohol, which was carried out for several generations. It is noted that some primates are more easily trained to choose alcohol in the free choice test - these animals evaluated the effect of opioid receptor antagonists. Both naloxone and naltrexone weakened or blocked the propensity to drink alcohol on these experimental models. Other studies have shown that alcohol activates the endogenous opioid system. The blockade of opioid receptors prevents the increase in the level of dopamine in the adjacent nucleus caused by alcohol use, that is, the work of the mechanism with which the reinforcing effect of alcohol is supposedly associated.

Naloxone

Thus, these experimental data served as the basis for subsequent clinical trials of naltrexone in alcoholics who were treated on a one-day program in a hospital setting. Naloxone - an opioid antagonist of short action - is poorly absorbed when taken orally. In contrast, naltrexone is fairly well absorbed from the intestine and has a high affinity for opioid receptors, and the duration of its action in the brain reaches 72 hours. In the initial controlled clinical trial, it was shown that, compared to placebo, naltrexone mostly blocks some of the reinforcing effects of alcohol and reduces craving for alcohol.

In the same study, it was shown that alcoholics taking naltrexone had significantly fewer relapses than those taking placebo. These results were confirmed by other investigators, and in 1995 the FDA approved the use of naltrexone for the treatment of alcoholism. Nevertheless, it was stressed that alcoholism is a complex disease, and naltrexone is better used in a comprehensive rehabilitation program. In some patients, the drug helps to significantly reduce the desire and weaken the effect of alcohol, if the patient "breaks down" and again begins to use it. Treatment should last at least 3-6 months, while the regularity of taking the drug should be controlled.

Acamprostate

Acamprostate is a derivative of homotaurin, which can also help in the treatment of alcoholism. The effectiveness of the drug has been proven in some experimental models of alcoholism and in double-blind clinical trials. According to experimental data, acamprostate acts on the GABAergic system, weakening post-alcohol hypersensitivity, and is also an NMDA receptor antagonist. It remains unclear why this action is useful in this situation, and whether the clinical effect of the drug is associated with it. In a large double-blind, placebo-controlled study, acamprostat had a statistically more significant effect than placebo. The drug has already been registered in several European countries. It is important to cancel that acamprostate has a completely different mechanism of action than naltrexone, which makes it possible to hope for the possibility of summing up their effect in a combined application.

[38], [39], [40], [41], [42], [43], [44]